The Stages of Hereditary Amyloidosis - Akcea Therapeutics

1. Understanding the Stages of hATTR Amyloidosis hATTR amyloidosis is the most common form of heredofamilial amyloidosis in familial amyloid polyneuropathies. However, the deposits of ATTR in the elderly primarily involving the heart consist of normal TTR (Transthyretin) without any mutation. The Manifestations of Polyneuropathy of Hereditary Amyloidosis hATTR amyloidosis comes in a wide variety of symptoms at different stages of life. Numbness, tingling, burning sensation, swelling, walking disability, loss of balance, orthostatic hypotension, erectile dysfunction is urinary retention are some of the many such known symptoms. Based on the Coutinho Staging System, patients suffering from hATTR amyloidosis can be classified into three stages of the disease based on the severity of symptoms and the extent of disease progression. Coutinho Staging System STAGE 0 In this stage, the patient is usually asymptomatic. Patients have the mutation in the TTR gene and show evidence of Amyloid deposits. STAGE 1 At Stage 1, the patient does not usually require any assistance with ambulation. Symptoms are mostly very mild and the disease is limited to the lower limbs. There are mild motor and autonomic neuropathy in the lower limbs, for instance, weakness of extensors in the big toes. This is the stage for early detection of FAP (Familial amyloid polyneuropathy) symptoms. Patients at this stage are ideal candidates for a liver transplant. In the case of hATTR amyloidosis, it’s important to note that individuals of Portuguese descent are at a higher risk of inheriting this rare disease than most other people. If you have Portuguese ancestry and any of your close family members have been previously diagnosed with it, then you may be at risk of getting it as well. Genetic testing is a crucial step in being correctly diagnosed.

2. STAGE 2 This is the stage where the patient may require assistance with ambulation. The disease progresses and the symptoms start to appear in the limbs (weakness and wasting of muscles). The patient is disabled but can move with help. There is a high chance of nerve damage due to the accumulation of amyloid. STAGE 3 At this stage 3, the patient is either wheelchair-bound or bedridden. There is severe sensory, motor, and autonomic neuropathy of all limbs with generalized weakness. Polyneuropathy Disability (PND) Scoring System Polyneuropathy Disability Scoring System (PND) is also a widely popular method to classify the progression of hATTR. PND l A patient on the PND l scale experiences sensory disturbances in their extremities. However, at this stage, the walking capacity is still preserved. PND ll At PND II there is difficulty in walking for the patient. However, at this point, there is still no need for a walking stick. PND lll-A At PND lll-A, the patient may require a walking stick or one crutch for walking. PND lll-B It is at this stage that the patient may require two walking sticks/crutches for walking. PND lV At PND IV, the patient is confined to a wheelchair or is bedridden.

3. Available Treatments hATTR amyloidosis is a serious (but treatable) condition. It is a rare disease and one which is very difficult to diagnose. Misdiagnosis is very common and it can take patients several years from the onset of symptoms to get the right diagnosis and start treatment. There are numerous treatments across different regions of the world where there is a significant Portuguese population. In Canada, TEGSEDI™ (inotersen solution for subcutaneous injection) is recommended for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR), and has shown promising results in treating the condition to a significant extent.